Our aim is to understand the structure-function relationship of tRNA by studying the role of the modified nucleosides in tRNA. Our objective is to establish, by x-ray diffraction techniques, the details of the stereochemistry of modified nucleosides in the monomeric and polymeric states and establish any conformational restrictions they might have on the conformation of tRNA. We will develop and evaluate proposals for the role of modified nucleosides in tRNA, particularly for modified bases in and adjacent to anticodons. We will investigate the details of the stereochemistry of codon-anticodon interaction. We shall study adenyl cytokinins and investigate their mechanism of action. We shall develop stereochemical criteria that will be of some help in developing a rational chemotherapy program involving modified bases, cytokinins and their analogs. We shall investigate the intercalation of water between nucleic acid bases and the consequences of such intercalation in nucleic acid replication.